Shiwei Qingwen decoction regulates TLR4/NF-κB signaling pathway and NLRP3 inflammasome to reduce inflammatory response in lipopolysaccharide-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Shiwei Qingwen decoction (SWQ), a Chinese herbal formula based on the classic traditional Chinese medicine prescription Yu Ping Feng San, has shown efficacy in preventing and treating early pneumonia with good clinical outcomes. However, its underlying mechanism is yet unclear. AIM OF THE STUDY: To clarify the preventive and therapeutic effects of SWQ on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore the underlying mechanism by which SWQ influences pneumonia. MATERIALS AND METHODS: First, the chemical composition of SWQ was preliminarily determined by high performance liquid chromatography (HPLC), and the impact of SWQ (3.27, 6.55, and 13.1 g/kg) was assessed in the LPS-induced ALI rat model. Next, its inflammatory pathway was determined via network pharmacology. Finally, the molecular mechanism of SWQ was validated using a rat ALI model and a THP-1 cell inflammation model. RESULTS: HPLC identified chlorogenic acid, prime-O-glucosylcimifugin, calycosin, and 5-O-methylaminoside in the chemical profile of SWQ. In the ALI model, SWQ alleviated ALI by reducing lung wet/dry weight ratio (W/D) and preventing histopathological damage to the lungs. At the same time, SWQ decreased penetration of inflammatory mediators by upregulating AQP1 and AQP5 and endothelial nitric oxide synthase (eNOS). Pretreatment with SWQ downregulated white blood cells and neutrophils count in BALF and suppressed LPS-induced expression levels of MPO, NE, and pro-inflammatory factors (TNF-α, IL-1ß, IL-6, and iNOS). Network pharmacology showed that SWQ was associated with TLR4/NF-κB inflammation pathway. Moreover, pretreatment with SWQ reduced the expression level of TLR4/NF-κB signaling pathway-associated proteins (TLR4, Myd88, p-IκB, and p-p65) and NLRP3 inflammasome (NLRP3, ASC, caspase-1, and cleaved-IL-1ß) in vivo and vitro. CONCLUSIONS: The present study demonstrates that SWQ can reduce inflammation in ALI by inhibiting TLR4/NF-κB and NLRP3 inflammasome activation.

Identification and Comparison of Tannins in Gall of Rhus chinensis Mill. and Gall of Quercus infectoria Oliv. by High-Performance Liquid Chromatography-Electrospray Mass Spectrometry.

Gall of Rhus chinensis Mill. (Chinese galls) and gall of Quercus infectoria Oliv. (Turkish galls) have similar applications and chemical compositions, and their extracts have been widely used for industrial production and for medicinal applications. In this study, high-performance liquid chromatography-electrospray mass spectrometry (HPLC-ESI-MS/MS) methods were established for profiling the components of Chinese galls and Turkish galls. Compounds representing 96.56 and 99.15% of the total peak area of Chinese galls and Turkish galls were identified. The results identified that the ellagic acid, galloyl-HHDP-glucose and pedunculagin act as the identifying markers for the comparison of Chinese galls and Turkish galls in HPLC-ESI-MS/MS. The peak area of tetragalloyl-glucoside, heptagalloyl-glucoside and pentagalloyl-glucoside can be used to distinguish these two phytomedicines. This work provides a reference for the study of the chemical composition of Chinese galls and Turkish galls, which not only introduce a simple and reliable method to prevent the adulteration or misuse of Chinese galls and Turkish galls but also lay the foundations for clarifying the material basis of their similar pharmacological action.

Hollow Microcapsules with Ulcerative Colitis Therapeutic Effects Made of Multifunctional Turkish Galls Extraction.

Ulcerative colitis (UC) has been listed as one of the refractory diseases of modern society by the World Health Organization. Our previous studies found that Turkish galls Gallotannins (TGTs) have a significant effect on anti-UC. Here, TGTs were extracted using a simple method and TGTs-FeIII microcapsules were prepared by a self-assembly technique. Microcapsules were characterized by liquid chromatography-mass spectrometry, scanning electron microscopy, and so forth. The results verified that hollow spheres of TGTs-FeIII microcapsules were successfully prepared. It is interesting that microcapsules were more likely to accumulate on the inflammatory surface from ex vivo and in vivo adhesion experiments, and effectively alleviate UC symptoms. This study will provide valuable insight into the development of safe and efficient drug delivery system platforms for further biomedical usages.

Screening for active constituents in Turkish galls against ulcerative colitis by mass spectrometry guided preparative chromatography strategy: in silico, in vitro and in vivo study.

Turkish galls have been reported to exhibit remedial effects in ulcerative colitis (UC). However, the active constituents of Turkish galls for the treatment of UC remain unclear. The objective of this study was to screen for anti-inflammatory active constituents and clarify their associated molecular mechanisms. Therefore, systems pharmacology was developed to predict the relationship between constituents and the corresponding targets as well as pathways. In addition, mass spectrometry-guided preparative chromatography technique was used for preparing constituents to evaluate the anti-inflammatory activities and the therapeutic efficacy against UC. In silico, active constituents exhibited a remedial effect on UC possibly by regulating multiple pathways and attacking multiple targets, of which those involved mainly in the NF-κB pathway were selected for verification. In vitro, 5 categories of constituents were screened as active constituents by comparing the cytotoxicity and detecting the level of the pro-inflammatory factors of 9 category constituents. In vivo, dextran sulfate sodium (DSS)-induced UC was significantly ameliorated in active constituents-fed mice. The results indicated that the active fraction comprising methyl gallate, digallic acid, di-O-galloyl-ß-d-glucose, and tri-O-galloyl-ß-d-glucose primarily contributed to the treatment of UC. Moreover, active fraction could also inhibit the phosphorylation level of IKKß, thus inhibiting the downstream NF-κB signaling pathway. The approach developed in this study not only clarifies the anti-inflammation effect of Turkish galls but also provides a beneficial reference for the discovery of the base material and functional mechanism of this herbal medicine.

Rosa rugosa flavonoids alleviate myocardial ischemia reperfusion injury in mice by suppressing JNK and p38 MAPK.

OBJECTIVE: Although Rosa rugosa has been applied for preventing coronary artery disease, the pharmacological mechanism is little explored. In this study, the effects and mechanisms of Rosa rugosa flavonoids (RRF) on myocardial ischemia reperfusion injury (MIRI) were investigated. METHODS: Mice were pretreated by intragastric administration of 600 mg/kg RRF for 7 days. Then MIRI was induced by 45 minutes coronary artery ligation and 3 hours reperfusion. Myocardial infarct size (MIS) and histopathology, activities of myocardial enzymes, and effects of RRF on inflammation and apoptosis were evaluated. RESULTS: Pretreating the mice with RRF significantly reduced MIS and inhibited activity of plasma myocardial enzymes. Activity of the enzymes associated with anti-oxidation, SOD, and TEAC, and mRNA expression of NOX2 were significantly elevated. RRF pretreatment significantly decreased the translocation of p65 from the cytoplasm into the nucleus and reduced the expression of the pro-inflammatory cytokines, IL-6 and IL-1ß. RRF pretreatment also significantly prevented the expression of caspase-3 and Bax, and increased the expression of Bcl-2. And RRF inhibited the phosphorylation of JNK and p38 MAPK. CONCLUSIONS: RRF significantly inhibited MIRI through anti-oxidative, anti-inflammatory, and anti-apoptosis effects, and mechanisms were associated with its inhibition on phosphorylation of JNK and p38 MAPK.